Giloy Ghanvati (Tinospora cordifolia (Willd.) Hook. f. and Thomson) Reversed SARS-CoV-2 Viral Spike-Protein Induced Disease Phenotype in the Xenotransplant Model of Humanized Zebrafish

Abstract

The current Severe Acute Respiratory Syndrome disease caused by Coronavirus-2 (SARS-CoV-2) has been a serious strain on the healthcare infrastructure mainly due to the lack of a reliable treatment option. Alternate therapies aimed at symptomatic relief are currently prescribed along with artificial ventilation to relieve distress. Traditional medicine in the form of Ayurveda has been used since ancient times as a holistic treatment option rather than targeted therapy. The practice of Ayurveda has several potent herbal alternatives for chronic cough, inflammation, and respiratory distress which are often seen in the SARS-CoV-2 infection. In this study we have used the aqueous extracts of Tinospora cordifolia (willd.) Hook. f. and Thomson in the form of Giloy Ghanvati, as a means of treatment to the SARS-CoV-2 spike-protein induced disease phenotype in a humanized zebrafish model. The introduction of spike-protein in the swim bladder transplanted with human lung epithelial cells (A549), caused an infiltration of pro-inflammatory immune cells such as granulocytes and macrophages into the swim bladder. There was also an increased systemic damage as exemplified by renal tissue damage and increased behavioral fever in the disease induction group. These features were reversed in the treatment group, fed with three different dosages of Giloy Ghanvati. The resultant changes in the disease phenotype were comparable to the group that were given the reference compound, Dexamethasone. These findings correlated well with various phyto-compounds detected in the Giloy Ghanvati and their reported roles in the viral disease phenotype amelioration.

Ayurvedic formulations: Potential COVID-19 therapeutics?

“…Importantly, Swasari Vati treatment showed progressive recovery of immune cell infiltration with very few pro-inflammatory infiltrates, suggesting its effectiveness in reducing the inflammatory damage caused by SARS-CoV-2 spike protein ( Balkrishna et al, 2020 ). In a similar study, T. cordifolia extract in the form of orally delivered powdered tablet, was also found to be effective in reversing the pathological symptoms in the zebrafish model ( Balkrishna et al, 2021b ).…”

“…Based on our searches, only five studies ( Balkrishna et al, 2021b ; Balkrishna et al, 2021c ; Balkrishna et al, 2020 ; Gheware et al, 2021a ; Upadhyay et al, 2020 ) have tested the ability of selected bioactive phytoconstituents of Ayurvedic herbs to directly bind and/or inhibit the function of SARS-CoV-2 proteins. Terminalia chebula is the major constituent of the Ayurvedic formulation known as Triphala and it has been reported to be beneficial in disease caused by herpes simplex virus-2 ( Kesharwani et al, 2017 ) and Influenza A virus ( Li et al, 2020 ).…”

“…Importantly, a herbal extract of W. somnifera enriched with withanone was able to ameliorate pathological symptoms in a zebrafish xenotransplant model that used the S protein as a marker for SARS-CoV-2 infection. The same group also investigated T. cordifolia ( Balkrishna et al, 2021b ) and Swasari Vati ( Balkrishna et al, 2020 ) as potential treatment options for COVID-19 using the zebrafish xenotransplant model. Swasari Vati is a calcium rich Ayurvedic mixture of 16 herbs or their extracts, processed into a tablet containing three excipients and is commonly prescribed for chronic cough, common cold and asthma.…”

“…A trial by Devpura et al (2021) in a geographically distant region of India (CTRI/2020/05/025273) compared the anti-COVID-19 efficacy of the same Ayurvedic treatment with placebo ( Devpura et al, 2021 ) and found that treatment was better than placebo in reducing time to a negative diagnostic test. Several phytoconstituents of both T. cordifolia and W. somnifera are predicted to bind to SARS-CoV-2 proteins S and M pro and the ACE2 receptor in molecular docking studies (refer to section above) and oral T. cordifolia treatment reversed pathology in a zebrafish xenotransplant model of COVID-19 ( Balkrishna et al, 2021b ). Interestingly, totality of evidence from in silico studies, animal models and clinical trials strongly suggest a multipronged mechanism underlying the observed effects of T. cordifolia on COVID-19.…”

Curcumin Extraction, Isolation, Quantification and Its Application in Functional Foods: A Review With a Focus on Immune Enhancement Activities and COVID-19

“…are present in plants such as Allium sativum, Curcuma longa, Ocimum tenuiflorum, Phyllanthus emblica, Piper nigrum, Tinospora cordifolia , etc. which contribute to their therapeutic characteristics, as presented in Table 1 ( 25 , 51 , 60 – 63 ). As found in previous studies, these plants are immunologically active, such as enhanced antibody production and macrophage mobility, cell-mediated immunity ( 64 ).…”